This renewal application is seeking support for a program that trains researchers to understand the links between chromosome metabolism and cancer. Recent advances in the studies of genes and genomes have greatly facilitated the understanding of chromosome metabolism and illustrated its importance in cancer cell formation and progression. The 27 training faculty are experts in this area from the Basic Sciences Division and the Human Biology Division of Fred Hutchinson Cancer Research Center. Many are leading scientists in their own fields, and together they form a cohesive group that approaches the issue from different but complementing angles. They include structural biologists in addition to molecular and cellular biologists, and utilize various model organisms such as nematode, fly, yeast in addition to vertebrates and cultured cells in their studies. The breadth and depth of this program should help generate excellent young scientists ready to deal with this complex problem. The program will continue to train at the predoctoral and postdoctoral levels. Three predoctoral positions are requested to maintain the current level of support of this successful program that was initiated five years ago following the formation of the Molecular and Cell Biology (MCB) Graduate Program. The postdoctoral positions will be expanded to six (from the current four positions) due to increased interests in this area and the expanded training faculty of the program (from 14 to 27). Predoctoral trainees will be recruited among the MCB students, who enter the joint program with the University of Washington, through vigorous competition and are among the best in the nation. Postdoctoral trainees will be recruited nationally. Training of predoctoral students includes course work, laboratory rotations and thesis research. Postdoctoral training will focus on independent research. All t r ainees will benefit from the rich activities available for cancer researchers at this Center. They will participate in weekly research group meetings, joint group meetings and Division meetings to report research findings to and exchange ideas with scientists within the lab, labs with similar interests, or the entire Divisions. They will also benefit from the strong interdisciplinary programs in the Center that expose basic scientists to clinical and public health aspects of cancer. In addition, they will have ready access to the newly formed patient care unit on campus. It is hoped that this program will train young scientists with in-depth understanding of chromosome metabolism and able to explore its various links to cancer cause, care and prevention.